Back in 1957, in his article published in Scientific American (volume 197, pp. 131–144), biologist Philip Siekevitz called the mitochondrion the ‘powerhouse of the cell’, a term very much used today when we talk about this complex organelle. Mitochondria are organelles that use oxygen and nutrients to generate energy and heat to maintain a stable body temperature. But did you ever wonder how hot they actually get when they ‘work’ to heat us up? A group of researchers did, and their findings are extraordinary: mitochondria can heat up to close to 50°C, even though our core temperature is closely maintained at 37.5°C.
Dominique Crétien, a researcher working with Pierre Rustin at the Université Paris 7 in France, along with a team of international researchers, decided to investigate how hot mitochondria actually get when they generate heat in healthy human cells. To do so, the authors used a brand-new dye that targets the mitochondria and changes its fluorescence with temperature, called MTY. When the researchers monitored the fluorescence of the dye during cellular respiration in a human kidney cell line, they found that mitochondria are able to function at temperatures that are approximately 10°C higher than the core body temperature. The group recorded this result multiple times and determined that, as long as the mitochondria are functional and have optimal conditions, they indeed increase their temperature during normal functioning.
Because of the controversial nature of their findings, Crétien and his colleagues decided to use various chemicals to impair mitochondrial function, while monitoring heat generation using the same fluorescent dye, in order to ensure that their results were real and not due to a faulty organelle or artifacts caused by the dye. To eliminate the possibility that the changes in MTY fluorescence were due to changes in pH and membrane potential of the mitochondria during respiration, the authors treated the human kidney cells with cyanide, oligomycin or respiratory enzyme inhibitors such as rotenone and antimycin – which are known to affect the mitochondria by altering membrane potential, changing the mitochondrial pH, disrupting membrane structure and affecting the function of the mitochondrial respiratory enzymes. Indeed, the authors found that MTY fluorescence correlated with mitochondrial respiration and that it was not due to faulty mitochondria or artifacts in the fluorescence. The researchers further validated their findings when the response of the dye was enhanced in the presence of proteins involved in heat generation. Therefore, MTY seems to work, and work well, when it comes to monitoring mitochondrial heat generation and mitochondria really do seem to run hot when they are generating energy.
Through their work, Crétien and his colleagues have raised even more questions about heat regulation in vertebrates. How can the mitochondrial enzymes perform so efficiently at such high temperatures? What implications do these findings have for mitochondrial structure and function? How do they affect (if at all) how we approach mitochondrial disorders and how we treat them? One thing is certain, though: the term ‘powerhouse’ just got a whole new meaning.
